Traumatic injury to the human body is perhaps the single most important contributor to long-term disability among working-aged persons in the industrialized world. Although many tissues are commonly fractured in traumatic injury, e.g., the liver, the kidney, the spleen and the testicle, perhaps the most often-injured tissues are the bones. I will discuss this invention in light of the treatment of bone fractures, recognizing that this invention can be applied to the treatment of other fractured tissues under appropriate circumstances.
The goals of bone fracture treatment are to stabilize healing fragments in anatomic alignment while allowing movement of surrounding muscles, thereby minimizing muscular atrophy during healing. Simple, transverse fractures are the quickest to heal, and it is with these that orthopedic surgery has been the most successful. However when a bone is shattered, even in 1993, the result is often permanent deformity and long term disability.
The two classes of internal fixation devices, i.e., appliances that are affixed to bone and left in the body during healing, currently in use are cortical compression plates and intrameduallary rods. These devices are very similar to those used over a century ago, and consequently do not take full advantage of the advances in our understanding of bone biology. A third class of orthopedic devices, the implantable prosthetics, has also been proposed (see U.S. Pat. Nos. 4,642,120 to Nevo-Svi, 1987 and No. 5,002,583 to Pitaru-Sandu, 1991). These devices are designed to become incorporated into host tissue after their implantation. These devices do incorporate biologic growth factors into their design but, for reasons I will discuss below, suffer from several disadvantages and consequently are not in widespread use.
It was recognized in the late 1800s that bone fractures healed faster when the proximal and distal ends were apposed. The compression plate, first described by Hansmann in 1886, is a rigid flat metal bar that is secured across a fracture with screws. Since its introduction, numerous configurations of the compression plate have been designed to improve the quality of fixation; however, since all involve securing the fracture with one or more rigid plates bound to the bone cortex, the adverse effects of the device on host bone are many. Three deserve mention, as they are major concerns in clinical practice.
First, although adequate for simple transverse fractures, a plate is unable to secure shattered bone because fragments are often small size and "free-floating" within the fracture cavity. Furthermore, multiple bone fragments are naturally resorbed ((biodegraded by host enzymes such that they are converted to their molecular form) unless they are held rigidly together. Fragment resorption is perhaps the most significant obstacle to healing comminuted fractures. Second compression plates remove virtually all stress where they are affixed such that the hardest bone, the cortex, often resorbs and becomes "spongified" increasing the risk of refracture. This effect is most pronounced the longer the plate is in place. Third, the longer a foreign body, e.g., a fixation device, is in place the greater the risk for infection. For these reasons, most orthopedic surgeons agree that, although the compression plate is useful, the less time it is affixed to host bone the better.
Recently, a malleable plate has been introduced for use of fractures involving curved surfaces, e.g., acetabular fractures. This plate is similar to the rigid plate in that it is metal; however it can be bent to better approximate segments of a curved bone such as the pelvis. Although a major advance, the malleable plate suffers from several limitations. First, it uses screws to hold together only the major fragments of the fracture, leaving the small fragments free to resorb. Second, it is of no additional benefit in the treatment of long bone fractures; and for the reasons stated above it may be a liability. Third, when the malleable plate is used alone, bone fragments are not held together when forces perpendicular to the long axis of the plate are applied.
A second class of internal fixation appliances is the intramedullary rod. Rod fixation involves pounding a long nail through the center of the bone, the medullary cavity, such that it bridges the fracture site. The advantages of rod fixation are maintenance of alignment and limb length, at least while the rod is in place. Although widely used, the intramedullary rod is poorly suited for comminuted fractures. The rod displaces fragments and severely compromises their blood supply, often resulting in resorbed fragments and non union. Furthermore, since small fragments surrounding the rod often resorb, the patient has a defect between proximal and distal fracture segments. Surgical intervention is subsequently required for bone grafting to maintain limb length.
A third type of fixation device has been proposed, the implantable fixed prosthetic device (see U.S. Pat. No. 5,002,583 to Pitaru-Sandu, 1991). These devices are composed of a rigid core surrounded by collagen that, once in the body, forms a biological bond with and integrates into host tissues. Although potentially suitable for affixing a prosthetic device to native bone, this device is poorly suited for treatment of fractures for at least three reasons: First, the device is rigid, making it impossible to modify if in the operating room to suit a specific need. Surgeons rarely know exactly the extent and dimensions of tissue injury until a fracture is exposed. Second, since these devices form an irreversible bond with the host tissue, fracture fragments resorb, causing native tissue to be replaced with prosthetic. Native tissue is always preferable to prosthetic, unless it is cancerous or is severely arthritic. Finally, foreign material, no matter of what it is composed, dramatically increases the risk of infection by blood-borne bacteria. Orthopedic surgeons almost universally agree that the sooner all prostheses are removed, the better. Implantable prosthetics, however, remain in the body for life.
In the case of implantable gels, e.g., U.S. Pat. No. 4,642,120 to Nevo-Svi, 1987, the gel is provided as an amorphous jelly which contains biologically active molecules and/or living cells. These gels are unsuitable for fractures for several reasons, of which three deserve mention as they severely limit their use in clinical practice. First, gels, even if supplied as a paste are unable to tightly bind fragments together. Fragments are then free to "float" around the cavity and out of the plane formed by the major fracture fragments. This often causes deformity and limb shortening when and if the fracture heals. Second, if the gel "hardens" once in place, native fracture fragments will be hindered in their ability to bridge among themselves by the intervening prosthetic. Thus, native fragments will be replaced by prosthetic as in the fixed prosthetic described above. Third, cells and/or medications are free to diffuse from the gel in all directions, often causing heterotopic (in the wrong place) bone formation. If a gel fragment lodges between muscle strands and forms bone around it, this could limit the use of that muscle forever.
Unfortunately, despite a century of advances in orthopedic surgery, the healing of severe fractures often occurs years later, in poor anatomic alignment and with considerable heterotopic bone formation within neighboring soft tissues. The lack success in repairing comminuted fractures stems from the fact that the problems of fragment resorbtion, cortical weakening during prolonged fixation, and diminution of bone blood supply during fixation have still not been adequately addressed by currently available orthopedic devices. An ideal fixation device would:
1) Hold the native fragments of a fracture in register such that they do not resorb. PA1 2) Deliver growth-promoting medications, e.g., bone morphogenetic proteins, angiogenic factors, nerve growth factors etc., directly and specifically to the injured tissues thereby preventing fragment resorbtion, and/or cell death, while minimizing reaction of neighboring tissues. PA1 3) Permit the surgeon to manipulate the device into the most advantageous configuration while in the operating room. PA1 4) Augment the function of and decrease the adverse effects (e.g., cortical "spongification") of existing classes of fixation devices such that fracture healing is quickened, permitting the rapid removal of fixation devices from the fracture site. PA1 5) Minimize heterotopic bone formation in soft tissues surrounding the fracture.
This invention meets these conditions by providing a malleable fixation device that, when wrapped around or affixed to fractured tissues, holds the fragments in tight register while delivering any of a number of medications directly and specifically to the fracture site. This invention is designed to be used with existing orthopedic devices that provide rigid fixation of major fracture fragments. With this invention heterotopic bone formation will be minimized, since both the exogenous (supplied by the invention) and endogenous (supplied by the native healing tissue) growth factors are directed preferentially into the fracture site. This invention is provided as a flexible two layered sheet that the surgeon in the operating room can staple, suture or otherwise affix to the injured site as each particular case demands.